New drug is effective in lowering LDL levels, but raises questions about drug pricing

Brenda Lau, 21 Mar 2017

Costing more than USD14,000 a year, insurers hesitate at paying without proof that evolocumab actually reduces the risk of death.

In 2015, two drugs were approved by the FDA for lowering low-density lipoprotein levels (LDL), preventing heart attacks and stroke. The two new drugs, evolocumab and alirocumab, have had their merits debated as they were based on basic science.

The drugs were distinctive as they simulated a favourable genetic variation and showed large reductions in the levels of bad cholesterol. Unlike statins, these drugs are administered through injections once or twice a month rather than daily pills.

However they were approved before large clinical trials were conducted, solely based on the ability to reduce LDL - which does not mean they are beneficial for patients. To prove their drugs, the companies producing these drugs conducted the clinical trials to determine if it improved outcomes.

Risk of heart attacks and stroke reduced by 15%

The first study, known as FOURIER, looked at Amgen's evolocumab, which had 27,564 international participants suffering from cardiovascular disease and were already consuming statins. The participants had an LDL level of about 90mg/dl when they first joined the study.

At the end of the two-year study, their LDL levels dropped to 30mg/dl, and the risk of cardiovascular events such as heart attacks and stroke, by 15%. One out of 66 individuals avoided these cardiovascular events. There were no obvious safety concerns about the drug, but there was no reduction in the risk of death.

Professor Peter Sever from Imperial College London, which led the UK branch of the study, said: "This is one of the most important trials of cholesterol-lowering since the first statin trial, published 20 years ago.

"Our results suggest this new, extremely potent class of drug can cut cholesterol dramatically, which could provide great benefit for a lot of people at risk of heart disease and stroke."

Doctors now have another tool to offer patients to reduce their risk, in this case, in patients whose cholesterol levels have been well-controlled by statins.

Dr. Marc Sabatine, the study leader, from Brigham and Women's Hospital in Boston says that for millions of people with heart disease or high risk for it like those in the study, "it's worth it to be on this medicine."

Is the drug worth its price?

But Dr. Donald Lloyd-Jones, preventive medicine chief at Northwestern University and an American Heart Association spokesman, called the results modest and "not quite what we hoped or expected."

The hope that cardiovascular disease would be eliminated by these drugs have been dimmed as the size of the benefit is less than what many would have predicted based on the steep decrease of LDL levels. The risk of deaths was also not reduced by the drug.

Mark Hlatky, a Stanford University cardiologist and cost effectiveness researcher, said, "people were hoping for a breakthrough, a lot bigger result than 20%."

Costing more than USD14,000 a year, insurers have also hesitated at paying without proof that it actually reduces the risk of death.

For patients like Susan Goodreds, whose insurance co-pay for evolocumab is USD356 a month, it is not a simple choice.

"It's an expensive, expensive drug," the 74-year-old Florida woman said. "You have to make some real decisions about whether to stay on it."

"That's the biggest issue — whether they're worth all the money," Hlatky said, referring to the drugs. He also raised a key question: if they cost 50 times as much as statins, "are they 50 times better? I don't think so."

For now, "we should still probably reserve these for the highest risk patients where statins are not doing a good enough job — at least at the price they are currently offered," said Lloyd-Jones.

Results proven, but monitoring still needs to be continued

Amgen has insisted that the drug's value justifies its cost and offered more deals for insurers, including a guarantee in the form of refunds for patients who have a heart attack or stroke after using evolocumab for at least six months.

In conclusion, the drug appears to be an effective agent and the reduction in risk is meaningful, however the benefit size is about the same as is achieved with statins.

But many questions still remain regarding the risk reduction in other populations and whether the injectable approach just provided a better outcome as there is no need to rely on patient compliance. There is also a need to monitor the participants as the long-term effects are still unknown.

For now, the drug just provides another option for patients and doctors to consider and insurance companies and other payers finally have a clear idea of what the drug benefits are and whether it is worth the price for each individual. MIMS

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